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Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for monitoring disease activity in inflammatory bowel disease (IBD). The aim of this study was to evaluate its utility in monitoring disease activity. In this retrospective study based on case records between August 2020 and July 2021 at our two centers, we examined the correlation between serum levels of LRG and C-reactive protein (CRP) with disease activity in IBD patients. Background factors related to serum LRG levels were also analyzed. Overall, 47 Crohn's disease (CD) and 123 ulcerative colitis (UC) patients were evaluated. In patients with CD, LRG and CRP levels correlated with Harvey-Bradshaw Index (HBI) and Simple Endoscopic Score for CD (SES-CD) (LRG and HBI, r = 0.397; LRG and SES-CD, r = 0.637; CRP and HBI, r = 0.253; CRP and SES-CD, r = 0.332). In patients with UC, LRG and CRP significantly correlated with the partial Mayo score (PMS) and Mayo endoscopic subscore (MES) (LRG and PMS, r = 0.3; CRP and PMS, r = 0.282; LRG and MES, r = 0.424; CRP and MES, r = 0.459). In CD patients with normal CRP, serum LRG level was significantly higher in those with mucosal inflammation than in those with mucosal healing (16.4 vs. 10.7 μg/ mL). Stenosis was associated with serum LRG levels in CD group using multiple regression analysis. Therefore, LRG is a useful biomarker for monitoring disease activity and mucosal inflammation, and indicates the status of intestinal stenosis in IBD patients.

Disruption of cancer screening programs and diagnoses of gastrointestinal cancers by the COVID-19 pandemic has been reported; however, little attention has been paid to the situation in depopulated areas with low infection rates. Akita Prefecture is one of the most depopulated areas of Japan and has the lowest COVID-19 infection rate per capita; at the same time, the prefecture has been top-ranked for mortality due to gastrointestinal cancer for years. In this population-based study in Akita Prefecture, we investigated the occurrence of gastrointestinal cancers and the number of cancer screening procedures over the five-year period of 2016-2020, employing a database from the collaborative Akita Prefecture hospital-based registration system of cancers. The occurrence of gastrointestinal cancers, especially esophago-gastric cancers, declined by 11.0% in 2020, when the COVID-19 pandemic affected the overall healthcare system, compared with the average of 2016-2019. Nonetheless, the occurrence of advanced-stage (stage IV) esophago-gastric cancers increased by 7.2% in 2020. The decrease in the gastrointestinal cancer diagnosis rate in 2020 coincided with a 30% decline in the total number of regular population-based screening programs. Under the ongoing COVID-19 pandemic, cancer screening was uniformly suspended throughout Japan. Accordingly, the COVID-19 pandemic has substantially disrupted the cancer screening system, leading to delays in diagnoses of gastrointestinal cancer, even in depopulated areas (Akita Prefecture) of Japan with a low prevalence of infection. Suspension of cancer screening procedures during an infectious disease pandemic should be thoroughly considered for each region based on the cancer incidence and infection status in that area.

OBJECTIVE To determine whether esophagectomy provides a survival advantage in octogenarians with resectable thoracic esophageal cancer. SUMMARY BACKGROUND DATA Elderly patients with thoracic esophageal cancer do not always receive the full standard treatment; however, advanced age alone should not preclude the use of effective treatment that could meaningfully improve survival. METHODS We retrieved the 2008-2011 data from the National Database of Hospital-based Cancer Registries from the National Cancer Center in Japan, divided the patients into a ≥75 group (75-79 years; n = 2,935) and a ≥80 group (80 years or older; n = 2,131), and then compared the patient backgrounds and survival curves. A multivariable Cox proportional hazards regression model was developed to compare the effects of esophagectomy and chemoradiotherapy in the two groups. RESULTS A significantly greater percentage of patients were treated with esophagectomy in the ≥75 group (34.6%) than the ≥80 group (18.4%). Among patients who received esophagectomy, the 3-year survival rate was 51.1% in the ≥75 group and 39.0% in the ≥80 group (P < 0.001). However, among patients who received chemoradiotherapy, there was no difference in survival curve between the two groups (P = 0.17). Multivariable Cox proportional hazard analysis revealed that esophagectomy for clinical Stage II-III patients was significantly associated to better survival (adjusted HR: 0.731) (95%CI: 0.645-0.829, p < 0.001) in the ≥75 group but not the ≥80 group when compared with CRT. CONCLUSIONS Many octogenarians do not necessarily get a survival benefit from esophagectomy. However, patients should be evaluated based on their overall health before ruling out surgery based on age alone.

We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study.We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative,2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C).Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS.ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).

Inflammatory myofibroblastic tumor is a rare intermediate-grade tumor. We herein report the case of an 81-year-old man with rectal ulceration and abnormal retroperitoneal soft tissue with a high serum level of IgG4. The administration of prednisolone reduced the retroperitoneal lesion; however, the rectal ulceration expanded. Surgical resection was performed. A histopathological examination revealed proliferating spindle cells accompanied by inflammatory cells and plasma cells. Liver metastasis emerged two months after surgical resection, and the histology of the proliferating spindle cells sampled by a fine-needle biopsy was similar to that of the rectal tissue. The patient ultimately died of inflammatory myofibroblastic tumor.

There are two distinct etiologies of esophago-gastric junctional adenocarcinomas (EGJACs): one associated with extensive gastric mucosal atrophy (GA), resembling non-cardiac gastric cancers; and the other related to gastro-esophageal reflux disease, resembling esophageal adenocarcinoma. In this study, we investigated the associations between the visceral fat area (VFA) and EGJACs separately in the two subtypes of EGJACs, depending on the extent of background GA. Sixty-four consecutive patients with EGJACs (Siewert type 2) were enrolled from a population-based database in Akita Prefecture, Japan, between 2014 and 2019. Two age- and sex-matched healthy controls were randomly assigned to each EGJAC case. The extents of GA were evaluated endoscopically, and the VFA values were measured based on computed tomography images. Logistic regression analyses were performed to investigate the associations between EGJACs and the VFA. Study subjects were classified into 2 subgroups depending on the extent of endoscopic GA: 29 (45.3%) without and 35 (54.7%) with extensive GA. Multivariable regression analyses revealed that a VFA of ≥100 cm2 was significantly associated with EGJACs in subjects without extensive GA [odds ratio (95% confidence interval): 2.65 (1.08–6.54)], while there was no such association in subjects with extensive GA [odds ratio (95% confidence interval): 1.52 (0.60–3.83)]. The contribution of the VFA to the etiology of EGJACs seems to differ depending on the extent of background GA, with the VFA more prominently associated with EGJACs in subjects without extensive GA than in those with it, providing further rationale concerning the heterogeneous nature of EGJAC etiology.

Mayo endoscopic subscore is a simple and validated endoscopic score for ulcerative colitis but the range of inflammation was not considered for scoring. There were few reports analyzing the range of inflammation for clinical relapse using Mayo endoscopic subscore (MES). The aim of this study is to investigate the relapsing potential of limited mucosal inflammation on endoscopic remission equivalent to MES of 0.For this retrospective observational study, ulcerative colitis patients underwent total colonoscopy were enrolled. Small mucosal lesion (SML) was defined as limited inflammation of range less than 3 cm. Clinical relapse was analyzed using the Kaplan-Meier curve with log-rank test, and factors associated with clinical relapse was analyzed using the cox proportional hazard regression model.A total of 102 periods with mucosal healing or modified MES of 0 with SML were analyzed. In 12-months observation periods, clinical relapse occurred more frequently in MES of 1 than in MES of 0 or modified MES of 0 with SML, but it was comparable between MES of 0 and modified MES of 0 with SML. When compared to patients with modified MES of 0 with SML, the hazard ratio in patients with MES of 1 (6.55;Small mucosal inflammation in UC does not affect the clinical relapse if most of the mucosa achieved a score similar to MES of 0.

While an association between esophago-gastric junctional adenocarcinomas (EGJACs) and obesity, especially visceral obesity, has been suggested in Western countries, the association remains unclear in Asia, including Japan. In this population-based case-control study, we investigated the association between EGJACs and obesity.To perform near-population-based data collection for all early-stage EGJACs occurring in Akita Prefecture from 2014 to 2019, clinical data, including endoscopic and computed tomography (CT) findings, were collected from 11 cancer treatment base hospitals in the area. Age- and gender-matched controls were extracted at a case-to-control ratio of 1:2 from healthy subjects who received health checkups in the same area. The visceral fat area (VFA) was calculated using CT images. Logistic regression analyses were performed to investigate the associations between EGJACs and obesity-related parameters.In total, 74 EGJAC cases (62 males, median age of 70 years old) and 148 controls were extracted. Multivariable analyses showed a significantly negative association between the BMI and EGJACs and a significantly positive association between the VFA and EGJACs with odds ratios (ORs) (95% confidence intervals [CIs]) of 0.65 (0.53-0.80) and 1.01 (1.01-1.02), respectively. These findings were confirmed in another dataset (40 EGJACs and 80 controls). In addition, as a categorical variable, VFA ≥ 100 cmWe found paradoxical associations between EGJACs and obesity-related parameters (BMI vs. VFA) in a Japanese population, suggesting a potentially pivotal role of the VFA rather than the BMI as a risk factor for EGJACs.

Background: Gastrointestinal bleeding (GIB) is one of the most common medical emergencies. We investigated the overall mortality after GIB in our institute and analyzed the prognostic factors in upper GIB (UGIB) and lower GIB (LGIB) separately. Summary: Between January 2010 and December 2018, 190 patients diagnosed with GIB in our hospital were retrospectively enrolled. Clinical records and biological data were collected. Risks for rebleeding and in-hospital mortality were assessed by a logistic regression analysis. Overall, the rebleeding rate and in-hospital mortality were 22.6 and 7.6%, respectively. GIB itself was not the direct cause of death in any cases. While older age (>65 years) was a significant risk factor for rebleeding in UGIB with an OR of 6.1 and 95% CI of 1.3–29.1, a poorer performance status (PS; ≥3) was a strong risk factor for rebleeding in LGIB, with an OR of 11.8 and 95% CI of 1.7–83.8. Poor PS and tachycardia (>100/min) were significantly associated with mortality in both UGIB and LGIB. In contrast, hypoalbuminemia (Key Messages: There were considerable differences in the risk factors for rebleeding and in-hospital mortality between UGIB and LGIB. The overall in-hospital mortality was 7.9% after GIB, including that a substantial portion of patients with GIB died from systemic complications after successful endoscopic hemostasis. Physicians need to diligently perform systematic treatment for GIB, which may be particularly important in societies of advancing aging, like Japan.

The incidence of peptic ulcers unrelated to H. pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs), termed idiopathic peptic ulcers (IPUs), has increased worldwide. We recently reported that IPUs were refractory to proton pump inhibitor (PPI) treatment. Vonoprazan, which was recently developed in Japan, has shown a more potent acid-inhibitory effect than ordinary PPIs. In the present study, we compared the healing rates among peptic ulcers of different etiologies following treatment with vonoprazan. A multicenter observational study was performed at six participating hospitals in Akita Prefecture, Japan. Consecutive patients who had endoscopically confirmed gastro-duodenal ulcers were enrolled between August 2016 and March 2018. For each patient, the Helicobacter pylori infection status and NSAID use, including aspirin, were checked, and 20 mg vonoprazan was administered for 6 weeks for duodenal ulcers and 8 weeks for gastric ulcers. The healing status was checked by endoscopy at the end of vonoprazan treatment. Patients were divided into four subgroups according to the H. pylori status and NSAID usage. The proportion of IPUs was 18.2%. A total of 162 patients completed the study protocol. The healing rate of IPUs was marginally lower than that of simple H. pylori-associated ulcers (81.2% vs. 93.5%, P = 0.05). Similarly, the healing rate of NSAID-related ulcers, irrespective of concomitant H. pylori infection, was significantly lower than that of simple H. pylori-associated ulcers. Six- or 8-week vonoprazan treatment still seems to be insufficient for healing IPUs. Longer-term vonoprazan or another treatment option may be required to heal potentially refractory peptic ulcers.

Introduction Proton pump inhibitors (PPIs) are associated with the onset of Clostridioides difficile infection (CDI). Although a new potassium-competitive acid blocker, vonoprazan, consistently shows a more potent acid inhibitory effect in comparison to PPIs, the risk of CDI in vonoprazan-treated patients relative to those treated with PPIs is unknown. In this retrospective case-control study, using a nationwide hospital-based administrative database in Japan, we investigated the association of the onset of CDI in patients treated with vonoprazan. Methods A CDI case was defined as a case in which a patient was diagnosed and treated for CDI. For each CDI case, 3 non-CDI patients were extracted as controls. Information on the usage of acid suppressants in the 2 months before the onset of CDI and other confounding factors was collected. Relative associations of gastric acid suppressants with the onset of CDI were estimated. Results A total of 4,466 CDI cases and 13,220 of non-CDI controls were extracted. A multivariate conditional regression analysis revealed that PPI or vonoprazan use was modestly, but significantly associated with CDI (odds ratio [95% confidence interval]: PPI, 1.3 [1.2-1.4]; vonoprazan, 1.4 [1.2-1.7]). With PPI users as a reference, vonoprazan did not show a stronger association with CDI (odds ratio [95% confidence interval]: 1.07 [0.91-1.26]). Discussion We found a significant positive association between vonoprazan use and CDI; however, the magnitude of the association was not beyond that in PPI users. This is the first report on any potential adverse effects of vonoprazan.

Background/Aims: 5-Aminosalicylic acid (5-ASA) is a basic drug for inducing and maintaining remission for ulcerative colitis. One of its formulations has a coating with a pH-dependent degradation that ensures the release 5-ASA at the terminal ileum. No evidence has been shown concerning the effects of proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs) on the clinical course of ulcerative colitis patients in remission. The present study assessed the effect of PPIs or H2RAs on the relapse of ulcerative colitis patients in clinical remission maintained by pH-dependent released 5-ASA.Methods: Ulcerative colitis patients who had been prescribed time- or pH-dependent-released 5-ASA between January 2015 and December 2018 were enrolled in this multicenter retrospective study. The period of remission until relapse occurred was analyzed among the patients taking time-dependent-released 5-ASA or pH-dependent-released 5-ASA with/without PPIs or H2RAs.Results: One hundred and nineteen patients were analyzed in this study. In the primary endpoint, the relapse rate was higher in patients taking pH-dependent-released 5-ASA and PPIs or H2RAs than in those taking the pH-dependent-released 5-ASA without PPIs or H2RAs, while the relapse rate was similar in patients taking the time-dependent-released 5-ASA with or without PPIs or H2RAs concomitantly. Patients with a short duration of disease and middle-aged patients more frequently showed relapse with PPIs or H2RAs than the other patients.Conclusions: The coadministration of PPIs or H2RAs affects the clinical course of ulcerative colitis in remission maintained by pH-dependent-released 5-ASA.

At present, squamous cell carcinoma accounts for most esophageal cancers in Japan; however, there is concern that the incidence of esophageal adenocarcinoma in Japan is increasing in comparison to Western countries. Akita Prefecture, with a population of 1 million, has the highest rate of esophageal cancer-associated mortality in Japan; the vast majority of these cases are squamous cell carcinoma. The aim of the present study was to investigate the latest trends in the incidence of esophageal adenocarcinoma in Akita Prefecture using a registration system. We examined the data from a collaborative hospital-based registration system for cancer patients. Eleven of the main hospitals in Akita Prefecture participate in this system, which covers 90% of the cancer cases in the region and which provides near population-based data. Using this registration system, we examined the sequential trends in the percentage of adenocarcinoma cases in relation to total esophageal cancer cases in Akita Prefecture from 2007 to 2014. In 2007–2014, a total of 2527 esophageal cancer patients were registered in the system. Among these, only 43 (1.8%) had adenocarcinoma. However, the number of adenocarcinoma patients gradually increased from 1 case in 2007 to 14 cases in 2014. Consequently, the percentage of adenocarcinoma cases showed a significant increase from 0.66% in the first 4 years of the study period to 2.5% in the latter 4 years of the study period (P

With the decreasing global trend in the Helicobacter pylori infection rate, compositional changes in the gastric cancer subsites have occurred worldwide. However, the compositional changes in Asian countries, including Japan, remain to be clarified. The aim of this study is to investigate the latest chronological changes in the gastric cancer subsite using a hospital-based registration system in Akita prefecture in Japan. From 2007-2015, subsites of gastric cancers were coded according to the International Classification of Diseases for Oncology (ICD-03). The nine-year registration period was divided into the three 3-year periods: 2007-2009, 2010-2012, and 2013-2015. A total of 10,804 cases of gastric cancer were registered. The proportion of cardiac cancer among total gastric cancer slightly but significantly declined from 12.1% in 2007-2009 to 9.2% in 2013-2015 (P < 0.01). Among non-cardia cancer, the proportion of corpus cancer significantly increased from 41.3% to 50.2% during the study period (P < 0.01), while that of antropylorus cancer significantly decreased from 37.6% to 34.3% (P < 0.05). Such compositional changes in the gastric cancer subsite were observed largely in men, regardless of the histologic subtype of cancer. With the decreasing H. pylori infection rate, compositional changes in the gastric cancer subsite are occurring in Japan. While the proportion of cardia and antropylorus cancer is declining, that of corpus cancer is increasing, indicating diverse etiology of gastric carcinogenesis depending on the subsites. Identifying the most common sites of occurrence, may help to improve the efficiency of screening for gastric cancer.

GOALS To investigate retrospectively the risk factors for synchronous and metachronous cancers in the upper gastrointestinal tract in patients with superficial esophageal squamous cell carcinoma (ESCC). BACKGROUND In patients who have received endoscopic resection (ER) for ESCC, synchronous and metachronous cancers are frequently detected not only in the esophagus but also in the head and neck area and the stomach. STUDY A total of 285 patients who received ER for superficial ESCC were enrolled in this analysis. These patients were periodically followed-up endoscopically. Cumulative occurrence rates of the metachronous second primary cancers were determined by Kaplan-Meier method. Risk factors for synchronous and metachronous cancers in the head and neck area and the stomach were determined by logistic regression analyses. RESULTS During a mean follow-up period of 76 months, the 5-year cumulative occurrence of metachronous esophageal, head and neck, and stomach cancer was 14.0%, 2.8%, and 4.1%, respectively. Although the presence of multiple lugol-voiding lesions in the esophagus was a significant risk factor for synchronous and metachronous head and neck cancers (odds ratio, 3.8; 95% confidence interval, 1.7-9.0), older age (>65 y) was a significant risk factor for synchronous and metachronous gastric cancer (odds ratio, 3.1; 95% confidence interval, 1.2-9.3). CONCLUSIONS The risk factors for the cooccurrence of head and neck cancer and that of gastric cancer in patients with ESCC differ. This information will likely be useful for managing patients who have been treated with ER for ESCC and who possess carcinogenic potential throughout the upper gastrointestinal tract.

We describe the case of a 74-year-old female with a mesenteric lymph node abscess caused by a Yersinia enterocolitica infection. She had been administered an immunosuppressive drug and was admitted to the hospital due to a high fever, right lower abdominal pain and advanced leukocytosis. We initially diagnosed her with lymphadenitis based on the symptoms and the imaging studies. However, conservative treatment with antibiotics did not yield any improvement, and abscess formation was suspected. Surgical treatment was performed, and the culture from the drainage fluid grew Y. enterocolitica. The histological findings suggested that an ulcerative lesion of the terminal ileum was the entry port of Y. enterocolitica. The pathogen infected the mesenteric lymph nodes and spread along the ileocecal lymphatic vessels, resulting in the formation of an abscess. We also provide a review of the previously published literature on lymph node abscesses due to Y. enterocolitica infections.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin induce gastric mucosal lesions in part by the activation of inflammatory cells and the production of proinflammatory cytokines. The activation of adenosine A(2A) receptors inhibits inflammation by increasing cyclic AMP in leukocytes and reducing both the production of various proinflammatory cytokines and neutrophil chemotaxis. The aim of present study was to determine whether administration of an orally active adenosine A(2A) receptor agonist (4-[3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-piperidine-1-carboxylic acid methyl ester; ATL-313) ameliorated indomethacin-induced gastric mucosal lesions in rats.Gastric lesions were produced by oral gavage of indomethacin (30 mg/kg). ATL-313 (1-10 microg/kg) was given orally just before the indomethacin administration.The ulcer index induced by indomethacin was significantly (50%) reduced by pretreatment with ATL-313 and this effect was blocked completely by the addition of equimolar ZM241385, a selective A(2A) receptor antagonist. The gastric content of myeloperoxidase (MPO) and proinflammatory cytokines was significantly reduced by 10 microg/kg ATL-313, but gastric mucosal prostaglandin 2 (PGE2) was not affected.We conclude that ATL-313 does not inhibit the mucosal damaging effect of indomethacin, but it does block secondary injury due to stomach inflammation. A(2A) agonists may represent a class of new therapeutic drugs for NSAID-induced gastric ulcers.

Primary enterolith is a rare condition that can induce ileus and intestinal perforation. We report the first case of a true primary enterolith treated by balloon-assisted enteroscopy. The patient presented with a small intestinal ileus. After its improvement following the insertion of an ileus tube, radiography with amidotrizoate sodium meglumine detected a round, movable defect in the ileum measuring 42 mm diameter. The patient was diagnosed with a primary enterolith based on her past history. The enterolith was fractured and removed using balloon-assisted enteroscopy. This case suggests that balloon-assisted enteroscopy may be an effective non-invasive treatment option for enteroliths.

Behҫet's disease (BD) is a chronic disorder involving multiple organ systems including the small and large intestines. A 46-year-old female diagnosed with intestinal BD presented with ileocecal perforation and diffuse peritonitis and subsequently underwent ileocolic resection with ileostomy. After surgery, she suffered from refractory para-ileostomal ulceration associated with BD. Most importantly, however, treatment with infliximab was significantly effective in healing the ulceration. This is the first report of para-ileostomal ulceration associated with BD successfully treated with infliximab, suggesting the possible use of infliximab as a therapeutic option for para-stomal ulcers related to BD.

We herein describe the case of a 51-year-old man with a duodenocolic fistula (DCF) caused by a stomal ulcer. The patient complained of watery diarrhea, dysgeusia and malnutrition. His medical history included distal gastrectomy with Billroth I reconstruction for duodenal ulcer perforation. A combination study using endoscopy and contrast imaging confirmed the presence of DCF. Laparotomic fistulectomy was performed, which resulted in the patient's recovery from diarrhea and malnutrition. The histological findings suggested that the fistula had originated from a stomal ulcer. In patients with chronic watery diarrhea of obscure origin following gastrectomy, DCF is a possible cause of the diarrhea.

We report a case of gastric hamartomatous inverted polyps that are a rare histological type of gastric polyp and difficult to diagnose. Gastric submucosal tumor was detected by upper gastrointestinal X-ray series in 37-year-old man. Endoscopy revealed a submucosal tumor (SMT) , which eroded with a depression on its surface in the fornix. Endoscopic ultrasonography showed a heterogeneous tumor in the third layer. Endoscopic submucosal dissection (ESD) was performed to resect the tumor completely. The pathological diagnosis was a gastric hamartomatous inverted polyp. The patient was later discharged without any complications. Hamartomatous inverted polyps without a stalk are classified as the SMT type because the tumor is inverted down growth into the submucosal layer, otherwise polyps with a stalk are classified as the polyp type. All of the polyps were resected endoscopically, however, surgical resection was performed for those of the SMT type, because it is difficult to remove this type completely by en-block resection using conventional EMR technique. ESD method may be indicated for SMT-type hamartomatous inverted polyps.

To the Editor Gastric carcinoid tumors are rare. Nevertheless, when they occur, they are often found in patients diagnosed as having type A gastritis [1]. In patients with type A gastritis, the development of carcinoids and the widespread hyperplasia of enterochromaffin-like cells are related to atrophic changes of fundic mucosa and the trophic action of subsequently raised serum gastrin levels. In the past gastrectomy was the treatment of choice for carcinoid tumors; however, recent reports have shown that multiple gastric carcinoid tumors associated with type A gastritis are indolent and recommend that patients should receive more conservative treatment [1, 2]. We herein present one case where multiple gastric carcinoid tumors with hypergastrinemia and type A gastritis regressed after renal transplantation. In November 2000, a 51-year-old woman presented with epigastric pain and she received upper gastrointestinal endoscopy in our hospital. Endoscopic examination revealed multiple gastric polyps in the body and funds (Fig. 1). The polyps, measuring between 1 and 15 mm, were covered by intact mucosa identical to the surrounding tissue. The intervening gastric mucosa appeared atrophic with a pale shiny lining and visible submucosal vessels. Biopsies were taken for a histopathology of the polyps. Biopsies of the polyps showed gastric carcinoid tumors (Fig. 2), cells were positive for chromogranin A, synaptophysin, and neuron-specific enolase. Serum gastrin level was over 3,000 pg/ml (normal 0–90). Serum serotonin and urine 5-HIAA levels were normal. Antiparietal cell antibody was negative. Helicobacter pylori serology was negative. The patient was diagnosed as having multiple type I gastric carcinoid tumors. The question was how to manage this case. The patient did not want to receive surgical treatment, such as a total gastrectomy or antrectomy, because she had already received hemodialysis treatment for chronic renal failure. Therefore,with agreement of the patient, we decided to do an endoscopic follow-up. We performed endoscopic examination at six-month intervals. Between 2000 and 2004, follow-up endoscopy showed that the polyps had the same size as on the initial picture, and a histological examination of biopsies specimens revealed a residual carcinoid tumor in the mucosal layer. In December 2004, she received renal transplantation. After renal transplantation, she was treated with corticosteroid ( prednisolone, 10 mg/day) and Tacrolimus (Prograf, 4 mg/day) to prevent kidney graft rejection. The endoscopic examination at three months after renal transplantation showed marked regression of the carcinoid tumors. Furthermore, the endoscopic examination at six months after renal transplantation showed complete regression of the disease, though the serum gastrin level was still high (over 3,000 pg/ml) (Fig. 3). The endoscopic examination showed no progression of tumors at the end of the follow-up. Gastric carcinoid tumors fall under the broad classification of foregut carcinoid tumors. However, it is well known that these tumors are clinically and biologically distinct from the carcinoid tumors involving the rest of the gastrointestinal tract. In 1993, Rindi et al. classified gastric carcinoid tumor into three subtypes, based on pathogenesis [3]: type I and type II gastric carcinoids develop under the trophic influence of gastrin, whereas type III carcinoids are M. Odashima (&) M. Otaka M. Jin Y. Horikawa T. Matsuhashi R. Ohba N. Mimori S. Koizumi N. Kinoshita T. Takahashi S. Watanabe Department of Gastroenterogy, Akita University School of Medicine, 1-1-1, Hondo, Akita city, Akita 010-8543, Japan e-mail: odashima@doc.med.akita-u.ac.jp

[Background and Aim] Since the technical advance and the development of new devices, endoscopic submucosal dissection (ESD) is widely utilized for the treatment of superficial esophageal squamous cell neoplasms (ESCNs). In the treatment of ESCNs without nodal metastasis, ESD achieves the similar clinical outcomes to those of esophagectomy and chemoradioherapy and is much less invasive than them. The intensive studies of histopathological analysis of surgically resected ESCNs have proven that the cases of non-invasive carcinoma (EP, carcinoma in situ) and intra-mucosal invasive carcinoma limited to the lamina propria mucosae (LPM) had an extremely low risks of lymph node and distant metastasis. Based on these findings, the Japanese guideline for the treatment of esophageal cancer states that both EP and LPM cases are suitable for ESD. On the other hand, the lymph node metastasis rate of ESCNs invading to the muscularis mucosae (MM) including both with and without lymphovascular invasion has been reported as 7-10 %. Thus, ESD treatment had not been positively recommended for MM cases. However, it is assumed that MM cases without lymphovascular invasion have no lymph node metastasis. Thus, there exists the possibility that MM cases without lymphovascular invasion can be suitable for ESD. In this study, therefore, we evaluated expanded ESD indication to the MM cases without lymphovascular invasion, by analyzing surgically resected specimens histopathologically and investigating the clinical outcomes both after surgery and ESD of MM cases without lymphovascular invasion. [Methods] MM cases without lymphovascular invasion surgically treated between January 2001 and December 2010 (11 cases) and those treated with ESD between January 2006 and August 2012 (30 cases) at Akita University Hospital were enrolled in this study. [Results] In the detailed histopathological analysis of the surgically resected specimens of 11 MM cases without lymphovascular invasion, no lymph node metastasis was detected. No recurrence or metastasis developed in any of these 11 cases until today. In the analysis of the ESD-treated, 30 MM cases were proven to have no lymphovascular invasion by the histopathological examination of the specimens endoscopically resectd en bloc. Then, no additional therapy such as chemoradiotherapy was performed for these cases. However, all of the 30 cases are still alive without recurrence or metastasis during the followup period (4-81 months, average 33.8 months). [Conclusion] Our current study elucidated that MM cases without lymphovascular invasion has no risk of lymph node metastasis, and clinical outcomes of the ESD-treated MM cases without lymphovascular invasion are extremely satisfactory. These data suggest that ESD indication for superficial ESCNs treatment can be expanded to the MM cases without lymphovascular invasion.